Abstract

Two unrelated OPA1 mutation carriers have been previously reported with a multiple sclerosis (MS) like illness, an association felt unlikely to be coincidental. We present the first family with two affected members with optic atrophy and an MS-like illness with an underlying OPA1 mutation. A 46-year-old lady (the proband) and her 50-year-old sister had both been previously diagnosed with MS following presentation with visual impairment and lower limb neurological symptoms. 3-Telsa magnetic resonance brain imaging showed white matter hyperintense areas in both patients. Cerebro-spinal fluid analysis showed unmatched oligoclonal bands in the proband. The women's father and paternal grandmother had severe visual impairment. OPA1 mutational analysis was initiated in light of the finding of bilateral optic atrophy and severe visual impairment in the proband and the family history of severe visual impairment. A pathogenic mutation was identified in the proband and her sister. We confirm previous suggestions that OPA1 mutations can be associated with an MS-like illness. OPA1 is a nuclear gene encoding a protein important in mitochondrial function. This association bears similarity to the link between Leber's hereditary optic neuropathy due to mDNA mutations and an MS-like illness. OPA1 mutational analysis should be considered in patients with features of MS, with bilateral optic neuritis not responding to steroids, or with a dominant family history of severe visual impairment.